Vaccination protects rats from methamphetamine-induced impairment of behavioral responding for food

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• 作者：Daniela R¨¹edi-Bettschen ; Sherri L. Wood ; Melinda G. Gunnell ; C. Michael West ; Rama R. Pidaparthi ; F. Ivy Carroll ; Bruce E. Blough ; S. Michael Owens
• 关键词：AMP ; (+)-amphetamine ; Cys ; L-cysteine ; FI ; fixed-interval schedule of behavioral reinforcement ; FR ; fixed-ratio schedule of behavioral reinforcement ; [3H]-METH ; (+)-[2&prime ; 6&prime ; -3H(n)]-methamphetamine ; HSMO9 ; the METH-like hapten (S)-N-(2-(mercaptoe
• 刊名：Vaccine
• 出版年：2013
• 出版时间：23 September, 2013
• 年：2013
• 卷：31
• 期：41
• 页码：4596-4602
• 全文大小：851 K

文摘

(+)-Methamphetamine (METH) addiction is a chronic disease that interferes with fundamental brain-mediated behaviors and biological functions like eating. These studies present preclinical efficacy and safety profiles for a METH conjugate vaccine (IC_KLH-SMO9) designed to treat METH abuse. IC_KLH-SMO9 efficacy and safety were assessed over a 16-week period by monitoring general health and stability of responding in a food maintained behavioral paradigm. Male Sprague-Dawley rats were trained to lever press for food reinforcers until stable behavior was established. Rats (n = 9/group) were then immunized with 100 ¦Ìg of a control antigenic carrier protein (IC_KLH-Cys) or IC_KLH-SMO9 in Alhydrogel? adjuvant, with booster immunizations at 4, 8 and 12 weeks. Health, immunization site and behavior were assessed daily. No adverse effects were found. During weeks 14-16, when antibody titers and METH affinity (K_d = 13.9 ¡À 1.7 nM) were maximal, all rats received progressively higher METH doses (0.3-3.0 mg/kg) every 3-4 days, followed by behavioral testing. Even though the lower METH doses from 0.3 to 1.0 mg/kg produced no impairment in food maintained behavior, 3.0-mg/kg in control rats showed significantly (p < 0.05) reduced response rates and number of reinforcers earned, as well as reduced food intake. In sharp contrast, the IC_KLH-SMO9 group showed no changes in food maintained behavior at any METH dose, even though METH serum concentrations showed profound increases due to anti-METH antibody binding. These findings suggest the IC_KLH-SMO9 vaccine is effective and safe at reducing adverse METH-induced effects, even at high METH doses.